Role of Macrophage Polarization in Acute Respiratory Distress Syndrome
Round 1
Reviewer 1 Report
This is the second version of manuscript. Authors have done lots of corrections. Some corrections may improve the manuscript.
Page 4 line 113
Is the hyphen (‐) necessary after subtitles "Based on anatomical regions- " and "Depending upon polarization it can be divided into -"?
Please add the figure’s legend to Figure 4.
Page 10, line 305 Please delete "are" after “be considered”.
line 306-307 Please delete dot or numbers.
Is it necessary to use both dots and numbers?
Please correct references according to the ACS style guide.
References should be described as follows
Journal Articles:
Author 1, A.B.; Author 2, C.D. Title of the article. Abbreviated Journal Name Year, Volume, page range.
Moreover, references number in the main text should be placed in square brackets [ ].
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The authors have addressed all my concerns . There are no further comments.
Author Response
Thank you for your encouraging words. We are obliged to you.
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
The review of Yamini B Tripathi and colleagues is focused in the role of macrophage polarization in ARDS.
Although the review does not include new findings in the field, the review contains interesting data concerning macrophages in ARDS that could make this work interesting for the field. However, included information is not accurate and should be revised. Also, the writing is redundant and not properly focused, which difficult the take home message.
Information concerning ARDS is not completely correct. Authors introduce a section named “Risk factors”, although these are not risk factors. Information about hypoxemia in ARDS definition should be introduced, and also ARDS phenotypes. Pathophysiology of ARDS should be properly explained. Present research is not only focused into the role of genetic factors. The writing of the section “biomarkers: severity and further… their clinical significance” does not provide any information and can be reduced, what is important is the table. Please revise the table, as surfactant A and B is released by ATII and ATI cells, and introduce a biomarker for macrophages.
The writing of section “macrophage: the innate…and innate lymphoid cells (ILCs)” has no sense in this section. Introduce in here what is a macrophage, which is its function and the different types of macrophages that exist M1, M2a, M2b, M2c and M2d. Revise all the information, as macrophages classification is not simple, in many diseases you can find both types; M1 and M2 macrophages, both of them have a role. In ARDS, as properly explained by authors, in the initial stage macrophages are more pro-inflammatory and in the resolution they become more anti-inflammatory. However, both M1 and M2 are important for both the injury and the resolution. Authors state that resident alveolar macrophages are M2 and recruited macrophages M1, please revise, this statement is not correct.
Concerning section “role in ALI/ARDS” lines 187-234 have no sense in here, it should be included in the macrophages/macrophage phenotypes section, and also, it has to be summarized.
The discussion section is not a discussion, is a conclusion, and the importance of both; M1 and M2 macrophages should be clarified.
I enclose some references that can help:
Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, Herridge M, Randolph AG, Calfee CS. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019 Mar 14;5(1):18. doi: 10.1038/s41572-019-0069-0. PMID: 30872586; PMCID: PMC6709677.
Thompson BT, Chambers RC, Liu KD. Acute Respiratory Distress Syndrome. N Engl J Med. 2017 Aug 10;377(6):562-572. doi: 10.1056/NEJMra1608077. PMID: 28792873.
Matthay MA, Arabi YM, Siegel ER, Ware LB, Bos LDJ, Sinha P, Beitler JR, Wick KD, Curley MAQ, Constantin JM, Levitt JE, Calfee CS. Phenotypes and personalized medicine in the acute respiratory distress syndrome. Intensive Care Med. 2020 Dec;46(12):2136-2152. doi: 10.1007/s00134-020-06296-9. Epub 2020 Nov 18. PMID: 33206201; PMCID: PMC7673253.
Aggarwal NR, King LS, D'Alessio FR. Diverse macrophage populations mediate acute lung inflammation and resolution. Am J Physiol Lung Cell Mol Physiol. 2014 Apr 15;306(8):L709-25. doi: 10.1152/ajplung.00341.2013. Epub 2014 Feb 7. PMID: 24508730; PMCID: PMC3989724.
Herold S, Mayer K, Lohmeyer J. Acute lung injury: how macrophages orchestrate resolution of inflammation and tissue repair. Front Immunol. 2011 Nov 24;2:65. doi: 10.3389/fimmu.2011.00065. PMID: 22566854; PMCID: PMC3342347.
Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010 May 28;32(5):593-604. doi: 10.1016/j.immuni.2010.05.007. PMID: 20510870.
Gordon S. The macrophage: past, present and future. Eur J Immunol. 2007 Nov;37 Suppl 1:S9-17. doi: 10.1002/eji.200737638. PMID: 17972350.
Bibliography has to be revised and actualized.
English mistakes have to be addressed.
Use ALI only in the context of animal studies and ARDS in the context of clinical studies
Reviewer 2 Report
It is known that macrophages play a key role in innate immunity and host defense, forming the first-line defense against infections. In the manuscript entitled “Role of Macrophage Polarization in Acute Lung Injury/Acute Respiratory Distress Syndrome”, the authors aimed to summarize the role of M1 and M2-polarized macrophages in the pathogenesis of ALI/ARDS. In the background, the authors detailed the symptoms, causes, categories, pathophysiology, and diagnostic biomarkers of ALI/ARDS, which may help the reader with limited knowledge of the disease. Besides, the general functions of macrophages in human physiology were described. Finally, the authors reviewed a few studies on macrophage polarization and ALI/ARDS. However, the manuscript is not well-organized and difficult to follow. Furthermore, it is impossible to summarize the role of macrophages and their polarization in ALI/ARDS using than 8 references.
- As a review article, most of the sentences lack supporting literature. For instance, from lines 64 to 82, only one reference was cited.
- In Figure 1, how did the authors make the conclusions? Are macrophages polarized to M2 during sepsis? All the figures are drawn without citing any references.
- Figures are not cited in the main text. Figure legends are needed for each of them.
- The section on Role in ALI/ARDS is not written logically. It is a simple summary of the previous publication one by one. Two paragraphs (lines 194 to 199, lines 273 to 279) are not associated with the topic.
Reviewer 3 Report
English must be checked by a native speaker, there are many grammatical and phraseological errors in the text. The sentences lack fluency, making the manuscript difficult to read
References
All references must change according to journal instruction. Moreover, references number in the main text should be placed in square brackets [ ].
The sign and symptoms of ARDS are epigrammatically presented. Please add text to this section.
Page 3 line 109
If you use general title for the chapter 7 (Macrophages), it will be rationale to continue this section with subtitles, for example 7.1 Types of macrophages.
Line 117
Please correct the name of Elie Metchnikoff.
line 130-131
Please delete the sentence "Depending on the site of action macrophages can be classified into followings (see 130 Table 4)" you just repeated the above paragraph.
Page 4 line 141
It is better to add as subtitle 7.2.
In addition, the title "Macrophages with respect to human physiology" is incorrect. Please change to "Physiological role of macrophages" or "Function of macrophages in diseases".
The sentence "They put an interesting fact on the anti-inflammatory effect of IL-10" does not sound scientifically correct.
Maybe you change this sentence to “The results of this study suggested that curcumin increased the anti-inflammatory effect of IL-10”.
Page 5 line 160
"Role in ALI/ARDS" The title is not completed.
Probably you mean the role of macrophages in ALI. Please complete
In this section you describe the role of macrophages in different phases of ALI, but unfortunately the phases of disease do not describe in the previous section about the pathophysiology of ALY Page 2 line 63-89.
Page 7 line 275. Please correct the phrase "the significance of level of between".
Line 28. Please add space after ALI/ARDS.
Reviewer 4 Report
The authors has made a good compilation and description on the role of macrophages in ALI/ARDS
